Chemistry of the Carbonyl Group

TIMOTHY K. DICKENS, FRSC, is Official Fellow, College Lecturer and Director of Studies in Chemistry at Peterhouse, Cambridge. Dr Dickens graduated from the University of Kent in 1982, and, after two years' research at Oxford, he joined Glaxo where he spent 24 years in both scientific and technology senior roles. In 2008, he joined the University of Cambridge, where his research has focused on Ring Currents in conjugated systems. STUART WARREN, PHD, is the author of the textbooks Organic Chemistry, Organic Synthesis: The Disconnection Approach and Organic Synthesis. He retired from Churchill College, Department of Chemistry, University of Cambridge in 2006, having fostered some of the most successful organic chemistry academics in the UK.

• Preface xiAcknowledgements xiiiSome Help That You May Need xvWhat Do You Need to Know Before You Start? xviiIntroduction xix1 Nucleophilic Addition to the Carbonyl Group 1Nucleophilic addition: what it is and how it happens 3Alcohols as nucleophiles: acetal formation 6Some carbon–carbon bond-forming reactions with carbon nucleophiles: cyanide ion, acetylide ion and Grignard reagents 10Hydride ion and its derivatives LiAlH4 and NaBH4 Reduction of aldehydes and ketones 17Meerwein–Ponndorf reduction and Oppenauer oxidation, with a branch program on how to draw transition states 19Two general revision problems 252 Nucleophilic Substitution 29Substitution: how it happens 31LiAlH4 reduction of esters 33Reaction of Grignard reagents with esters 34Alkaline hydrolysis of esters 38Acid hydrolysis of amides 39Summary of acid and base catalysis 41Reaction between carboxylic acids and thionyl chloride 41Synthesis of esters and anhydrides from carboxylic acids 43Review questions 453 Nucleophilic Subsitution at the Carbonyl Group with Complete Removal of Carbonyl Oxygen 49Imine formation from aldehydes and ketones 51Oxime formation and the structure of oximes 53Hydrazone and semicarbazone formation 54Reduction of C=O to CH2 56Conversion of C=O to CCl2 60DDT synthesis 64Chloromethylation of aromatic compounds 65Review questions 664 Carbanions and Enolisation 69Carbanions 71Tautomerism 72Equilibration and racemisation of ketones by enolisation 73Halogenation of ketones 78Formation of bromo-acid derivatives 83Organo-zinc derivatives and their use in synthesis 85Review questions 875 Building Organic Molecules from Carbonyl Compounds 89Using enols as nucleophiles to attack other carbonyl groups 92The aldol reaction 92The Claisen ester condensation 93Acid catalysed condensation of acetone 94Self-condensation reactions 96Elaboration of a skeleton in synthesis 97Cross-condensations with molecules which cannot enolise 98Mannich reaction 103Perkin reaction 105Stable enols from β-dicarbonyl compounds 108Knoevenagel reaction 110Alkylation of β-dicarbonyl compounds 113Michael reaction 116Decarboxylation 125Base cleavage of β-dicarbonyl compounds 131Cyclisation reactions: the Dieckmann condensation 134Cyclisation of diketones 136The dimedone synthesis 137Ring opening by base cleavage of β-dicarbonyl compounds 141Revision questions 142Examples of syntheses: two steroid syntheses 145Stork’s cedrene synthesis 150Index 155